Oxazolidinedione-type compounds were prepared for the first time by reacting N-ethoxycarbonyl-glycine with thionyl chloride and heating the acyl chloride intermediate at 85° C. to yield the corresponding cyclic anhydride (Leuchs, Chem. Ber., 39, 1906, 858). This reaction is demonstrated on FIG. 1 in Reaction Scheme 1.
There are several processes known according to the state of the art for the preparation of the compounds of the general Formula (II). Usually amino acids of the general Formula (IV) are used as starting compounds.
Oxazolidinediones of the general Formula (II) are prepared by the reaction of the amino acids of the general Formula (IV) and phosgene derivatives. The reaction products were often not isolated, even their formation was not mentioned, but said intermediates were reacted immediately in situ in a peptide coupling reaction. Likewise, in the first process directed to the preparation of N-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-4-(S)-methyl-oxazolidine-2,5-dione (compound of general Formula (II) wherein R1 is phenyl, R2 is ethyl), the mixture of N-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanine (compound of Formula (IV), wherein R1 is phenyl, R2 is ethyl) and N,N′-carbonyl-diimidazole was refluxed in nitrogen atmosphere for 15 minutes and the solution thus obtained was directly used in subsequent reaction steps (Jerry W. Skiles, Raymond D. Youssefyeh, John T Suh, Howard Jones EP 61768, 29 Mar. 1982). This process is demonstrated on FIG. 2 in Reaction Scheme 2.
Oxazolidinediones of the general Formula (II) were prepared, isolated and characterized by other authors in a similar way by using N,N′-carbonyl-diimidazole (Oudenes, Jan y Schleicher, Richard Henry ES 2004804, 1 Feb. 1989; Marjo Mrslavic, Janja Crinski U.S. Pat. No. 5,359,086, 16 Sep. 1993).
According to a frequently used process also known according to the state of the art, oxazolidinediones of the general Formula (II) are prepared by reacting the amino acid of the general Formula (IV) and phosgene (Fu-chih Huang, Howard Jones, Clara J. Lin, Bernard Loev EP 114067, 12 Jan. 1983; Raymond D. Youssefyeh, Jerry W. Skiles, John T. Suh, Howard Jones, U.S. Pat. No. 4,686,295, 7 Mar. 1983; Satomi Takahashi, Kenji Inoue, Yoshyfumi Yanagida, Takehisa Ohashi, Kiyoshi Watanabe EP 215335, 23 Aug. 1986).
Another known process utilizes trichloromethyl chloroformate as a further phosgene derivative for the preparation of oxazolidinediones of the general Formula (II) (Satomi Takahashi, Kenji Inoue, Takehisa Ohashi, Kiyoshi Watanabe U.S. Pat. No. 4,716,235, 29 Dec. 1987).
According to a still further known process, the less toxic triphosgene has been used instead of phosgene (Pau Cid EP 1279665 23 Jul. 2002)
According to a further known process, the compounds of the general Formula (IV) were transformed into compounds of their N-alkoxy(aralkoxy)-carbonyl derivatives of the general Formula (V)
and said derivatives were used for the preparation of the compounds of general Formula (II).
European Patent No. 1 197 490 (inventors: Chong-Ming Chen, Yu-Liang Liu, Ya-Chieh Chai, Chien-Huang Wu. application date, 15 May 2001.) discloses the reaction between the amino acids of general Formula (IV) (wherein R1 represents phenyl and R2 represents ethyl) and 1.2 molar equivalents of ethyl chloroformate in dichloroethane, whereupon the compound of general Formula (V) thus formed (wherein R1 is phenyl and R2 and R3 each represents ethyl) was reacted with a carboxyl group activating reagent, e.g. thionyl chloride, acetyl chloride or acetic anhydride to yield the corresponding oxazolidinedione of general Formula (II). This process is demonstrated on FIG. 3 in Reaction Scheme 3.